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Krey, K.* ; Risso-Ballester, J.* ; Hamad, S.* ; Maidl, S.* ; Bilekova, S.* ; Emslander, Q.* ; Verin, M. ; Mundigl, S.* ; Cernat, A.* ; Piras, A.* ; Bergant, V.* ; Grass, V.* ; Pichlmair, A.

The ISG Atlas: A loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.

Nat. Commun. 17:4206 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The innate immune system requires the activity of interferon-stimulated genes (ISGs) to mount its protective response against viruses. However, the activity of ISGs against viruses varies widely and is orchestrated by the interplay of hundreds of ISGs. Utilizing a time-resolved, arrayed loss-of-function screen, we systematically investigate 285 ISGs for their virus-modulating activity against eight viruses. The quantitated data from the screen results do not necessarily result in similar quantitative biological effects of gene function but indicates virus specificity of many ISGs and pan-proviral activity of some ISGs, such as RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB). Co-depletions of selected candidates identify ISGs with synergistic functions, highlighting particularly strong synergies between ISGs inhibiting entry pathways and ISGs involved in IFN signaling. Among unexplored ISGs, we identify BORCS8, which has a particularly prominent role in modulating SARS-CoV-2 infection. Mechanistically, BORCS8 mediates the acidification of early endosomes during viral entry, a process known to facilitate the degradation of virus particles. Collectively, this extensive resource reveals specificities of ISGs identified in this screening system and suggests potential strategies for antiviral treatment options.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Interferon ; Innate Immune System ; Gene ; Endosome ; Virus ; Function (biology) ; Interferon-stimulated Gene
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 17, Heft: 1, Seiten: , Artikelnummer: 4206 Supplement: ,
Verlag Springer
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen Danmarks Grundforskningsfond (Danish National Research Foundation)
Deutsche Forschungsgemeinschaft (German Research Foundation)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)